Estetrol and Mammary Gland: Friends or Foes?

Estrogens have pleiotropic effects on many reproductive and non-reproductive tissues and organs including the mammary gland, uterus, ovaries, vagina, and endothelium. Estrogen receptor α functions as the principal mediator of estrogenic action in most of these tissues. Estetrol (E4) is a native fetal estrogen with selective tissue actions that is currently approved for use as the estrogen component in a combined oral contraceptive and is being developed as a menopause hormone therapy (MHT, also known as hormone replacement therapy). However, exogenous hormonal treatments, in particular MHTs, have been shown to promote the growth of preexisting breast cancers and are associated with a variable risk of breast cancer depending on the treatment modality. Therefore, evaluating the safety of E4-based formulations on the breast forms a crucial part of the clinical development process. This review highlights preclinical and clinical studies that have assessed the effects of E4 and E4-progestogen combinations on the mammary gland and breast cancer, focusing in particular on the estrogenic and anti-estrogenic properties of E4. We discuss the potential advantages of E4 over current available estrogen-formulations as a contraceptive and for the treatment of symptoms due to menopause. We also consider the potential of E4 for the treatment of endocrine-resistant breast cancer.

A Micronutrient Mixture may Reduce the incidence and Improve the Effectiveness of Drug Therapy of Alzheimer’s Disease

Costus species is a significant restorative and decorative plant used to fix various illnesses. In India 6,000 plants are used for traditional and herbal medicine. The plant Costus spicatus commonly known as ‘Spiral ginger’ as ‘insulin plant’, a wonder drug down blood sugar level and hypoglycemic properties. The plant has been found to have numerous pharmacological exercises, for example, antibacterial, antifungal, anticholineesterase, cancer prevention agent, antihyperglycemic, calming, pain relieving, antipyretic, antidiuretic, antistress and estrogenic action. The rhizomes of Costus species are harsh, astringent, bitter, cooling, love potion, laxative, anthelminthic, depurative, febrifuge, expectorant, tonic, improve assimilation, and is an energizer herb that clears poisons. It additionally has against richness, anabolic properties. This audit plainly demonstrates the need to perform logical investigations with therapeutic vegetation featuring potential for Costus species because of its antidiabetic, pharmacological and cell reinforcement properties. The rhizome is credited with purgative and tonic properties. India is a botanical garden of the world for natural resources.

A Literature Review of Anti- Diabetic Medicinal Plant Properties (Costus speices)

Costus species is a significant restorative and decorative plant used to fix various illnesses. In India 6,000 plants are used for traditional and herbal medicine. The plant Costus spicatus commonly known as ‘Spiral ginger’ as ‘insulin plant’, a wonder drug down blood sugar level and hypoglycemic properties. The plant has been found to have numerous pharmacological exercises, for example, antibacterial, antifungal, anticholineesterase, cancer prevention agent, antihyperglycemic, calming, pain relieving, antipyretic, antidiuretic, antistress and estrogenic action. The rhizomes of Costus species are harsh, astringent, bitter, cooling, love potion, laxative, anthelminthic, depurative, febrifuge, expectorant, tonic, improve assimilation, and is an energizer herb that clears poisons. It additionally has against richness, anabolic properties. This audit plainly demonstrates the need to perform logical investigations with therapeutic vegetation featuring potential for Costus species because of its antidiabetic, pharmacological and cell reinforcement properties. The rhizome is credited with purgative and tonic properties. India is a botanical garden of the world for natural resources.

Previous estradiol treatment during midlife maintains transcriptional regulation of memory-related proteins by ERα in the hippocampus in a rat model of menopause

Previous midlife estradiol treatment, like continuous treatment, improves memory and results in lasting increases in hippocampal levels of estrogen receptor (ER) α and ER-dependent transcription in ovariectomized rodents. We hypothesized that previous and continuous midlife estradiol act to specifically increase levels of nuclear ERα, resulting in transcriptional regulation of proteins that mediate estrogen effects on memory. Ovariectomized middle-aged rats received estradiol or vehicle capsule implants. After 40 days, rats initially receiving vehicle received another vehicle capsule (Vehicle). Rats initially receiving estradiol received either another estradiol (Continuous Estradiol) or a vehicle (Previous Estradiol) capsule. One month later, hippocampal genes and proteins were analyzed. Continuous and previous estradiol increased levels of nuclear, but not membrane or cytosolic ERα and had no effect on Esr1. Continuous and previous estradiol impacted gene expression and/or protein levels of mediators of estrogenic action on memory including ChAT, BDNF, and PSD-95. Findings demonstrate a long-lasting role for hippocampal ERα as a transcriptional regulator of memory following termination of previous estradiol treatment in a rat model of menopause.

Natural and Synthetic Estrogens Regulate Human Health

Estrogen are very important chemical compounds very essential for our body functions. The cholesterol, what we eat through food, gets converted by the action of various enzymes. Scientists have synthesized estrogenic molecules in the laboratory and used them for oral contraceptives and other therapeutic purposes. Environmental estrogenic molecules (xenestrogen) played havocs in human life. Plants also make estrogenic substances (phytoestrogen); they are very useful for mankind. All steroid hormones, including estrogen are synthesized from cholesterol through a common precursor steroid, pregnenolone which is formed by the enzymatic cleavage of a 6-carbon side-chain of the 27-carbon cholesterol molecule. Cholesterol is a starting substance of group of estrogenic compounds [1]. On the other hand, synthetic estrogen are compounds obtained by chemical synthesis that possess estrogenic activity [2]. In addition to these estrogenic compounds there are some estrogenic action mimicking compounds known as xenestrogen and phytoestrogen (Figure 1).

Isoflavones Protective Mechanisms Against Cardiovascular Diseases

Isoflavones are polyphenolic compounds and a class of phytoestrogens naturally present in plants belongs to legume family and also quantified in fruits, vegetables and beverages.Soybean is rich source of isoflavones. Their chemical structure is similar to endogenously available female reproductive hormonal substance estradiol,and cellular targets are estrogen receptors. After bind to the estrogen receptors isoflavones exert estrogenic and anti-estrogenic action based upon circulatory levels of estradiol. Cardiovascular diseases are leading cause of death in most of the developing countries and they may occur due to the structural and functional changes in either cardiac muscle or smooth muscle of the vasculature and both. Common cardiac diseases are heart attack, coronary heart disease, hyperlipidaemia, angina pectoris, hypertension. Many epidemiological studies data revealing that consumption of soy protein and soy enriched diet correlate with preventive chances of cardiovascular disease. The United States Food and Drug Administration (USFDA) and other countries declared that everyday consumption of food enriched soy along with low fat may decrease the risk of cardiovascular disease. In this review we attempt the mechanism based cardioprotection of isoflavones in different cardiovascular diseases.

Letrozole: an emerging array of hope for infertile women

Ovulation induction has been a major breakthrough in the management of female infertility since many decades. Letrozole, an aromatase inhibitor has been used as a potential therapy for ovulation induction. A large number of clinical evidences have been emerging which cite the beneficial role of Letrozole in conditions like anovulatory infertility, polycystic ovary syndrome (PCOS), unexplained infertility and an incipient role in endometriosis- related infertility with regards to higher live-birth rates. Letrozole is a superior alternative to Clomiphene citrate (CC) which has been used conventionally as ovulation inducer. Clomiphene citrate has certain well-defined disadvantages, whereas Letrozole overcomes these limitations to a reasonable extent. The peripheral anti-estrogenic effect of CC leads to prolonged depletion of estrogens receptors, adversely affecting endometrial growth and development as well as quantity and quality of cervical mucus. Persistent blockade of estrogen receptor leads to CC resistance and is associated with reduced ovulation and pregnancy rates. Available evidences suggest Letrozole is superior to CC owing to the lack of persistent anti-estrogenic action due to its short half- life and lack of action on estrogen receptors. This typically leads to monofollicular growth and also higher live birth rates. The current evidences suggest that Letrozole can be placed as first line therapy for the management of infertility due to PCOS and unexplained infertility.

Fenugreek seeds estrogenic activity in ovariectomized female rats

The estrogenic activities of fenugreek seeds (Trigonella foenum-graecum L.), widely used in traditional pharmacopoeia, are reflected in the uterus of ovariectomized female rats, with a slight increase in dry and wet weight, a thickening of the stroma and the uterine epithelium and the development of the endometrial glands. In the vagina, the estrogenic action is shown through an increase in the epidermal cell number and a tendency to keratinization, leading to vaginal opening. Furthermore, this estrogenic potential of fenugreek seeds is confirmed by the over-expression of progesterone receptors in the uterine tissues supporting possible interactions between phytoestrogens and estrogen receptors. Therefore, Fenugreek seeds may be capable of promoting the development of reproductive tissues of immature ovariectomized rats, and its estrogenic activity may take its action by holding phystoestrogens that interact with estrogen binding sites and activate the same estradiol-mediated cell signaling pathways. Thus, our results give added scientific support to the popular use of Fenugreek seeds as an alternative for several health problems such as fertility and menopause related disorders.